The Global Framework for the Progressive Control of Transboundary Animal Diseases - Strengthening Infectious Disease Management and Veterinary Systems Across the Continents: Origins and Testimony.

Transboundary animal diseases are defined by the Food and Agriculture Organization (FAO) of the United Nation's Emergency Prevention System as those diseases that are of significant economic, trade and/or food security importance, which can easily spread to other countries and reach epidemic proportions, and where control/management including exclusion requires cooperation among several countries. The Global Framework for the Progressive Control of Transboundary Animal Diseases represents a platform of the FAO and World Organisation for Animal Health to engage regional sub-regional organizations and national veterinary authorities in developing and monitoring progress in animal disease management efforts.

A longitudinal study of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in humans in 2012. Since then, 2605 cases and 937 associated deaths have been reported globally. Camels are the natural host for MERS-CoV and camel to human transmission has been documented. The relationship between MERS-CoV shedding and presence of neutralizing antibodies in camels is critical to inform surveillance and control, including future deployment of camel vaccines. However, it remains poorly understood. The longitudinal study conducted in a closed camel herd in Egypt between December 2019 and March 2020 helped to characterize the kinetics of MERS-CoV neutralizing antibodies and its relation with viral shedding. RESULTS: During the 100-day longitudinal study, 27 out of 54 camels (50%) consistently tested negative for presence of antibodies against MERS-CoV, 19 (35.2%) tested positive and 8 (14.8%) had both, positive and negative test results. Fourteen events that could be interpreted as serological indication of probable infection (two seroconversions and twelve instances of positive camels more than doubling their optical density ratio (OD ratio) in consecutive samples) were identified. Observed times between the identified events provided strong evidence (p = 0.002) against the null hypothesis that they occurred with constant rate during the study, as opposed to clustering at certain points in time. A generalized additive model showed that optical density ratio (OD ratio) is positively associated with being an adult and varies across individual camels and days, peaking at around days 20 and 90 of the study. Despite serological indication of probable virus circulation and intense repeated sampling, none of the tested nasal swab samples were positive for MERS-CoV RNA, suggesting that, if the identified serological responses are the result of virus circulation, the virus may be present in nasal tissue of infected camels during a very narrow time window. CONCLUSIONS: Longitudinal testing of a closed camel herd with past history of MERS-CoV infection is compatible with the virus continuing to circulate in the herd despite lack of contact with other camels. It is likely that episodes of MERS-CoV infection in camels can take place with minimal presence of the virus in their nasal tissues, which has important implications for future surveillance and control of MERS-CoV in camel herds and prevention of its zoonotic transmission.

Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

Seasonality and Ecological Suitability Modelling for Anthrax (Bacillus anthracis) in Western Africa.

Anthrax is hyper-endemic in West Africa affecting wildlife, livestock and humans. Prediction is difficult due to the lack of accurate outbreak data. However, predicting the risk of infection is important for public health, wildlife conservation and livestock economies. In this study, the seasonality of anthrax outbreaks in West Africa was investigated using climate time series and ecological niche modeling to identify environmental factors related to anthrax occurrence, develop geospatial risk maps and identify seasonal patterns. Outbreak data in livestock, wildlife and humans between 2010 and 2018 were compiled from different sources and analyzed against monthly rates of change in precipitation, normalized difference vegetation index (NDVI) and land surface temperature. Maximum Entropy was used to predict and map the environmental suitability of anthrax occurrence. The findings showed that: (i) Anthrax outbreaks significantly (99%) increased with incremental changes in monthly precipitation and vegetation growth and decremental changes in monthly temperature during January-June. This explains the occurrence of the anthrax peak during the early wet season in West Africa. (ii) Livestock density, precipitation seasonality, NDVI and alkaline soils were the main predictors of anthrax suitability. (iii) Our approach optimized the use of limited and heterogeneous datasets and ecological niche modeling, demonstrating the value of integrated disease notification data and outbreak reports to generate risk maps. Our findings can inform public, animal and environmental health and enhance national and regional One Health disease control strategies.

A systematic approach toward progressive improvement of national antimicrobial resistance surveillance systems in food and agriculture sectors.

The first Food and Agriculture Organization of the United Nations (FAO) Action Plan on antimicrobial resistance (AMR), published in 2016, identified the need to develop capacity for AMR surveillance and monitoring in food and agriculture sectors. As part of this effort, FAO has developed the "Assessment Tool for Laboratories and AMR Surveillance Systems" (FAO-ATLASS) to assist countries in systematically assessing their AMR surveillance system in food and agriculture. FAO-ATLASS includes two different modules for surveillance and laboratory assessment. Each module includes two questionnaires that collect either qualitative or semi-quantitative data to describe and score the performance of national AMR surveillance system data production network, data collection and analysis, governance, communication and overall sustainability in a standardized manner. Based on information captured in the questionnaire by trained assessors (1) tables and figures describing the outputs of the surveillance system are automatically generated (2) a Progressive Improvement Pathway (PIP) stage, ranging from "1-limited" to "5-sustainable", is assigned to each laboratory assessed in the country, each area of the surveillance system and also to the overarching national AMR surveillance system. FAO-ATLASS allows national authorities to implement a strategic stepwise approach to improving their AMR surveillance systems via the FAO-ATLASS PIP system and provides an evidence base for actions and advocacy. The implementation of FAO-ATLASS at regional and global levels can contribute to harmonize and better coordinate strategies aimed at implementing an integrated AMR surveillance system under the One Health approach.

A literature review of the use of environmental sampling in the surveillance of avian influenza viruses.

This literature review provides an overview of use of environmental samples (ES) such as faeces, water, air, mud and swabs of surfaces in avian influenza (AI) surveillance programs, focussing on effectiveness, advantages and gaps in knowledge. ES have been used effectively for AI surveillance since the 1970s. Results from ES have enhanced understanding of the biology of AI viruses in wild birds and in markets, of links between human and avian influenza, provided early warning of viral incursions, allowed assessment of effectiveness of control and preventive measures, and assisted epidemiological studies in outbreaks, both avian and human. Variation exists in the methods and protocols used, and no internationally recognized guidelines exist on the use of ES and data management. Few studies have performed direct comparisons of ES versus live bird samples (LBS). Results reported so far demonstrate reliance on ES will not be sufficient to detect virus in all cases when it is present, especially when the prevalence of infection/contamination is low. Multiple sample types should be collected. In live bird markets, ES from processing/selling areas are more likely to test positive than samples from bird holding areas. When compared to LBS, ES is considered a cost-effective, simple, rapid, flexible, convenient and acceptable way of achieving surveillance objectives. As a non-invasive technique, it can minimize effects on animal welfare and trade in markets and reduce impacts on wild bird communities. Some limitations of environmental sampling methods have been identified, such as the loss of species-specific or information on the source of virus, and taxonomic-level analyses, unless additional methods are applied. Some studies employing ES have not provided detailed methods. In others, where ES and LBS are collected from the same site, positive results have not been assigned to specific sample types. These gaps should be remedied in future studies.

Base protocol for real time active random surveillance of coronavirus disease (COVID-19) - Adapting veterinary methodology to public health.

The pandemic of new coronavirus disease COVID-19 is threatening our health, economy and life style. Collaborations across countries and sectors as a One Health World could be a milestone. We propose a general protocol, for setting timely active random surveillance of COVID-19, at the human community level, with systematic repeated detection efforts. Strengths and limitations are discussed. If considered applicable by public health, the protocol could evaluate the status of COVID-19 epidemics consistently and objectively.

Surveillance to improve evidence for community control decisions during the COVID-19 pandemic - Opening the animal epidemic toolbox for Public Health.

During the first few months of 2020, the COVID-19 pandemic reached Europe and spread around the world. Health systems all over the world are trying to control the outbreak in the shortest possible time. Exotic disease outbreaks are not uncommon in animal health and randomised surveillance is frequently used as support for decision-making. This editorial discusses the possibilities of practicing One Health, by using methods from animal health to enhance surveillance for COVID-19 to provide an evidence base fort decision-making in communities and countries.

Eradication of Peste des Petits Ruminants Virus and the Wildlife-Livestock Interface.

Growing evidence suggests that multiple wildlife species can be infected with peste des petits ruminants virus (PPRV), with important consequences for the potential maintenance of PPRV in communities of susceptible hosts, and the threat that PPRV may pose to the conservation of wildlife populations and resilience of ecosystems. Significant knowledge gaps in the epidemiology of PPRV across the ruminant community (wildlife and domestic), and the understanding of infection in wildlife and other atypical host species groups (e.g., camelidae, suidae, and bovinae) hinder our ability to apply necessary integrated disease control and management interventions at the wildlife-livestock interface. Similarly, knowledge gaps limit the inclusion of wildlife in the FAO/OIE Global Strategy for the Control and Eradication of PPR, and the framework of activities in the PPR Global Eradication Programme that lays the foundation for eradicating PPR through national and regional efforts. This article reports on the first international meeting on, "Controlling PPR at the livestock-wildlife interface," held in Rome, Italy, March 27-29, 2019. A large group representing national and international institutions discussed recent advances in our understanding of PPRV in wildlife, identified knowledge gaps and research priorities, and formulated recommendations. The need for a better understanding of PPRV epidemiology at the wildlife-livestock interface to support the integration of wildlife into PPR eradication efforts was highlighted by meeting participants along with the reminder that PPR eradication and wildlife conservation need not be viewed as competing priorities, but instead constitute two requisites of healthy socio-ecological systems.

Field evaluation of common poultry viral vaccinesin Egypt: a need for reassessment of the vaccine value chain.

Egypt has a large traditional and exotic poultry sector which is challenged regularly by poultry diseases in endemic and epidemic proportions. The household poultry in particular is a source of livelihoods and employment for millions of low income citizens. Highly pathogenic avian influenza (HPAI) H5N1 and Newcastle disease are the most important poultry diseases in this sector. Whereas poultry vaccines are available to reduce the incidence of disease in Egypt, their effectiveness is doubtful. We conducted a biological evaluation of selected viral vaccines of poultry in three governorates in Egypt. Fifty­four percent of the vaccines had reduced vaccine titres and the effect of secondary vaccine distributions was associated with the observed vaccine titres. External contamination was observed in some vaccines and break in cold chain was reported. Whereas no vaccine distributor used purpose­built vaccine refrigerator, none also had prescribed protocol for vaccine handling or kept record of vaccine. There is a need to review vaccine handling procedure, monitor of vaccine cold chain more critically and review the whole chain that support vaccine distributions in Egypt.

Mapping Potential Amplification and Transmission Hotspots for MERS-CoV, Kenya.

Dromedary camels have been implicated consistently as the source of Middle East respiratory syndrome coronavirus (MERS-CoV) human infections and attention to prevent and control it has focused on camels. To understanding the epidemiological role of camels in the transmission of MERS-CoV, we utilized an iterative empirical process in Geographic Information System (GIS) to identify and qualify potential hotspots for maintenance and circulation of MERS-CoV, and produced risk-based surveillance sites in Kenya. Data on camel population and distribution were used to develop camel density map, while camel farming system was defined using multi-factorial criteria including the agro-ecological zones (AEZs), production and marketing practices. Primary and secondary MERS-CoV seroprevalence data from specific sites were analyzed, and location-based prevalence matching with camel densities was conducted. High-risk convergence points (migration zones, trade routes, camel markets, slaughter slabs) were profiled and frequent cross-border camel movement mapped. Results showed that high camel-dense areas and interaction (markets and migration zones) were potential hotspot for transmission and spread. Cross-border contacts occurred with in-migrated herds at hotspot locations. AEZ differential did not influence risk distribution and plausible risk factors for spatial MERS-CoV hotspots were camel densities, previous cases of MERS-CoV, high seroprevalence and points of camel convergences. Although Kenyan camels are predisposed to MERS-CoV, no shedding is documented to date. These potential hotspots, determined using anthropogenic, system and trade characterizations should guide selection of sampling/surveillance sites, high-risk locations, critical areas for interventions and policy development in Kenya, as well as instigate further virological examination of camels.

Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016.

A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels.

Predominance and geo-mapping of avian influenza H5N1 in poultry sectors in Egypt.

Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype has been enzootic in the Egyptian poultry with significant human infections since 2008. This work evaluates the epidemiological and virological information from February 2006 to May 2015 in spatial and temporal terms. Only data with confirmed HPAI H5N1 sub-type were collected, and matched with the epidemiological data from various spatially and temporally-dispersed surveillances implemented between 2006 and 2015. Spatio-temporal analysis was conducted on a total of 3338 confirmed H5N1 HPAI poultry disease outbreaks and outputs described based on transmission patterns, poultry species, production types affected, trade, geographic and temporal distributions in Egypt. The H5N1 virus persists in the Egyptian poultry displaying a seasonal pattern with peak prevalence between January and March. There was no specific geographic pattern, but chickens and ducks were more affected. However, relatively higher disease incidences were recorded in the Nile Delta. Phylogenetic studies of the haemagglutinin gene sequences of H5N1 viruses indicated that multiple clusters circulated between 2006 and 2015, with significant deviations in circulation. Epidemiological dynamics of HPAI has changed with the origins of majority of outbreaks shifted to household poultry. The persistence of HPAI H5N1 in poultry with recurrent and sporadic infections in humans can influence virus evolution spatio-temporally. Household poultry plays significant roles in the H5N1 virus transmission to poultry and humans, but the role of commercial poultry needs further clarifications. While poultry trading supports the persistence and transmission of H5N1, the role of individual species may warrant further investigation. Surveillance activities, applying a multi-sectoral approach, are recommended.

Added Value of Avian Influenza (H5) Day-Old Chick Vaccination for Disease Control in Egypt.

The immunity profile against H5N1 highly pathogenic avian influenza (HPAI) in the commercial poultry value chain network in Egypt was modeled with the use of different vaccination scenarios. The model estimated the vaccination coverage, the protective seroconversion level, and the duration of immunity for each node of the network and vaccination scenario. Partial budget analysis was used to compare the benefit-cost of the different vaccination scenarios. The model predicted that targeting day-old chick avian influenza (AI) vaccination in industrial and large hatcheries would increase immunity levels in the overall poultry population in Egypt and especially in small commercial poultry farms (from <30% to >60%). This strategy was shown to be more efficient than the current strategy of using inactivated vaccines. Improving HPAI control in the commercial poultry sector in Egypt would have a positive impact to improve disease control.

Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus.

In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.

Phylodynamics of avian influenza clade 2.2.1 H5N1 viruses in Egypt.

BACKGROUND: Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are widely distributed within poultry populations in Egypt and have caused multiple human infections. Linking the epidemiological and sequence data is important to understand the transmission, persistence and evolution of the virus. This work describes the phylogenetic dynamics of H5N1 based on molecular characterization of the hemagglutinin (HA) gene of isolates collected from February 2006 to May 2014. METHODS: Full-length HA sequences of 368 H5N1 viruses were generated and were genetically analysed to study their genetic evolution. They were collected from different poultry species, production sectors, and geographic locations in Egypt. The Bayesian Markov Chain Monte Carlo (BMCMC) method was applied to estimate the evolutionary rates among different virus clusters; additionally, an analysis of selection pressures in the HA gene was performed using the Single Likelihood Ancestor Counting (SLAC) method. RESULTS: The phylogenetic analysis of the H5 gene from 2006-14 indicated the presence of one virus introduction of the classic clade (2.2.1) from which two main subgroups were originated, the variant subgroup which was further subdivided into 2 sub-divisions (2.2.1.1 and 2.2.1.1a) and the endemic subgroup (2.2.1.2). The clade 2.2.1.2 showed a high evolution rate over a period of 6 years (6.9 × 10(-3) sub/site/year) in comparison to the 2.2.1.1a variant cluster (7.2 × 10(-3) over a period of 4 years). Those two clusters are under positive selection as they possess 5 distinct positively selected sites in the HA gene. The mutations at 120, 154, and 162 HA antigenic sites and the other two mutations (129∆, I151T) that occurred from 2009-14 were found to be stable in the 2.2.1.2 clade. Additionally, 13 groups of H5N1 HPAI viruses were identified based on their amino acid sequences at the cleavage site and "EKRRKKR" became the dominant pattern beginning in 2013. CONCLUSIONS: Continuous evolution of H5N1 HPAI viruses in Egypt has been observed in all poultry farming and production systems in almost all regions of the country. The wide circulation of the 2.2.1.2 clade carrying triple mutations (120, 129∆, I151T) associated with increased binding affinity to human receptors is an alarming finding of public health importance.